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Pentobarbital induces nocifensive hyperreflexia, not hyperalgesia in rats

David P. Archer, MD^*, Naaznin Samanani, BSc^* and Sheldon H. Roth, PhD^*,

^* From the Departments of Anesthesiology, and
Pharmacology and Therapeutics, Faculty of Medicine, The University of Calgary, Calgary, Canada.

Address correspondence to: Dr. David P. Archer, Department of Anesthesiology, Foothills Medical Center, 1403 29th St. N.W., Calgary, Alberta, Canada T2N 2T9. Phone: 403-670-1991; Fax: 403-670-2425; E-mail: archerd{at}cadvision.com

Purpose: To seek behavioural, reflexive and histochemical evidence of long-lasting changes in nociceptive stimulus transmission induced by exposure to doses of pentobarbital that induce nocifensive hyperreflexia.

Methods: Nocifensive hyperreflexia was induced in 12 rats with 30 mg•kg^–1 pentobarbital ip. Reflex latency times for withdrawal of the hind paw from noxious radiant heat were measured with an automated electronic timer. Subjective responses to noxious stimulation (licking or biting of the stimulated hindpaw) and the level of sedation were recorded. Histological sections of lumbar spinal cord were stained for immunoreactivity of the immediate-early-gene (IEG), c-fos, in three rats that received repeated threshold noxious radiant heat stimulation during the period of nocifensive hyperreflexia induced by 30 mg•kg^–1 pentobarbital ip.

Results: Reflex withdrawal latency decreased by 32 ± 8% of control values (P < 0.001) following pentobarbital injection and returned to control values 120 min after drug injection. Once fully alert, pentobarbital-treated animals did not show any increase in nociceptive behaviour relative to saline-injected controls (P = 0.41). Sustained noxious stimulation to the hindpaw in halothane-anesthetized animals was associated with an increase in c-fos immunoreactivity in the dorsal horn of the lumbar spinal cord ipsilateral to the stimulation (P < 0.001). Threshold stimulation in the pentobarbital-treated animals was not associated with any increase in c-fos expression.

Conclusions: During pentobarbital-induced hyperreflexia, rats did not show any reflexive, behavioural, or histochemical evidence of long-lasting enhancement of nocifensive signal transmission. The results are consistent with previous observations that, in the absence of tissue injury, nocifensive hyperreflexia induced by barbiturates is a short-lived pharmacological effect.

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